Tetraspanin CD53 Promotes Lymphocyte Recirculation by Stabilizing L-Selectin Surface Expression

Maria C Demaria; Louisa Yeung; Rens Peeters; Janet L Wee; Masa Mihaljcic; Eleanor L Jones; Zeyad Nasa; Frank Alderuccio; Pamela Hall; Brodie C Smith; Katrina J Binger; Gunther Hammerling; Hang Fai Kwok; Andrew Newman; Ann Ager; Annemiek van Spriel; Michael J Hickey; Mark D Wright

doi:10.1016/j.isci.2020.101104

Tetraspanin CD53 Promotes Lymphocyte Recirculation by Stabilizing L-Selectin Surface Expression

iScience. 2020 May 22;23(5):101104. doi: 10.1016/j.isci.2020.101104. Epub 2020 Apr 27.

Authors

Maria C Demaria¹, Louisa Yeung², Rens Peeters³, Janet L Wee², Masa Mihaljcic¹, Eleanor L Jones¹, Zeyad Nasa¹, Frank Alderuccio¹, Pamela Hall⁴, Brodie C Smith⁴, Katrina J Binger⁵, Gunther Hammerling⁶, Hang Fai Kwok⁷, Andrew Newman⁸, Ann Ager⁸, Annemiek van Spriel³, Michael J Hickey⁴, Mark D Wright⁹

Affiliations

¹ Department of Immunology and Pathology, Monash University, Alfred Research Alliance, Melbourne, VIC 3004, Australia.
² Department of Immunology and Pathology, Monash University, Alfred Research Alliance, Melbourne, VIC 3004, Australia; Centre for Inflammatory Diseases, Monash University Department of Medicine, Monash Medical Centre, 246 Clayton Road, Clayton, VIC 3168, Australia.
³ Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
⁴ Centre for Inflammatory Diseases, Monash University Department of Medicine, Monash Medical Centre, 246 Clayton Road, Clayton, VIC 3168, Australia.
⁵ Department of Biochemistry and Genetics, La Trobe Institute for Molecular Sciences, La Trobe University, Bundoora, VIC 3086, Australia.
⁶ Molecular Immunology, German Cancer Research Center, Heidelberg, Germany.
⁷ Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Taipa, Macau SAR, China.
⁸ Institute of Infection and Immunity, School of Medicine, Cardiff University, Cardiff CF14 4XN, UK.
⁹ Department of Immunology and Pathology, Monash University, Alfred Research Alliance, Melbourne, VIC 3004, Australia. Electronic address: mark.wright@monash.edu.

Abstract

Tetraspanins regulate key processes in immune cells; however, the function of the leukocyte-restricted tetraspanin CD53 is unknown. Here we show that CD53 is essential for lymphocyte recirculation. Lymph nodes of Cd53^-/- mice were smaller than those of wild-type mice due to a marked reduction in B cells and a 50% decrease in T cells. This reduced cellularity reflected an inability of Cd53^-/- B and T cells to efficiently home to lymph nodes, due to the near absence of L-selectin from Cd53^-/- B cells and reduced stability of L-selectin on Cd53^-/- T cells. Further analyses, including on human lymphocytes, showed that CD53 stabilizes L-selectin surface expression and may restrain L-selectin shedding via both ADAM17-dependent and ADAM17-independent mechanisms. The disruption in lymphocyte recirculation in Cd53^-/- mice led to impaired immune responses dependent on antigen delivery to lymph nodes. Together these findings demonstrate an essential role for CD53 in lymphocyte trafficking and immunity.

Keywords: Immune Response; Immunology; Molecular Mechanism of Behavior; Specialized Functions of Cells.

Abstract

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